Bactericidal and anti-quorum sensing activity of repurposing drug Visomitin against <i>Staphylococcus aureus</i>

With the growing antibiotic resistance in <i>Staphylococcus aureus</i>, it is imperative to develop innovative therapeutic strategies against new targets to reduce selective survival pressures and incidence of resistance. In <i>S. aureus</i>, interbacterial communication relies on a quorum sensing system that regulates gene expression and physiological activities. Here, we identified that Visomitin, an antioxidant small molecule, exhibited bactericidal efficacy against methicillin-resistant <i>S. aureus</i> and its high tolerance phenotypes like intracellular bacteria and persister cells without inducing resistance. Critically, sub-minimal inhibitory concentrations (sub-MICs) of Visomitin could serve as a potent quorum-quencher reducing virulence production (such as haemolysin and staphyloxanthin), along with inhibiting biofilm formation, self-aggregation, and colony spreading of <i>S. aureus</i>. These effects were probably mediated by interfering with the <i>S. aureus</i> accessory gene regulator quorum sensing system. In summary, our findings suggest that Visomitin shows dual antimicrobial effects, including bactericidal effects at the concentrations above MIC and quorum sensing inhibition effects at sub-MICs, which holds promise for treating MRSA-related refractory infections.